Clin Chem Lab Med 2007;45(10):1332–1338  2007 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2007.285 2007/106 Article in press - uncorrected proof Differentiating transudative from exudative pleural effusion: should we measure effusion cholesterol dehydrogenase? Mathie P.G. Leers*, Henne A. Kleinveld and Volkher Scharnhorst a Department of Clinical Chemistry and Hematology, Atrium Medical Center Heerlen, Heerlen, The Netherlands Abstract Introduction: Pleural effusions are often classified into transudates and exudates based on Light’s criteria. In this study, the diagnostic properties of Light’s criteria were compared to those of several other analytes for the classification of pleural fluids into transudative and exudative. Methods: A total of 471 patients with pleural effusions were evaluated. In pleural effusions and simultan- eously drawn blood samples, lactate dehydrogenase (LDH), total protein, albumin, cholesterol, amylase, glucose, pH and the cell number were measured. Ret- rospectively, the clinical records were used to estab- lish a clinical diagnosis. The diagnostic properties of the biochemical tests were calculated using the clini- cal diagnoses as gold standard. Results: By clinical diagnosis, 108 patients had transu- dative and 300 patients had exudative pleural effu- sions. In addition to pleural LDH activity (accuracy 89%, sensitivity 86%, specificity 97%) and fluid to serum LDH ratio (accuracy 89%, sensitivity 91%, spec- ificity 85%), pleural cholesterol concentration readily identified exudates (accuracy 82%, sensitivity 76%, specificity 98%). Combination of these three para- meters achieved a higher overall accuracy (accuracy 95%, sensitivity 93%, specificity 100%) than the Light’s criteria (accuracy 93%, sensitivity 100%, spec- ificity 73%). Combination of effusion cholesterol con- centration and effusion LDH activity had the highest discriminatory potential (accuracy 98%, sensitivity 98%, specificity 95%). Conclusions: Including effusion cholesterol, concen- tration in the routine biochemical work-up of pleural fluid allows for correct classification of more pleural effusions than achieved by use of Light’s criteria. Combination of cholesterol and LDH had the highest discriminatory potential and the added advantage that no patient plasma is needed for correct classification. Clin Chem Lab Med 2007;45:1332–8. Present address: Catharina Hospital, Clinical Laboratory, a Eindhoven, The Netherlands *Corresponding author: Mathie P.G. Leers, PhD, Department of Clinical Chemistry and Hematology, Atrium Medical Center Parkstad, P.O. Box 4446, 6401 Heerlen, The Netherlands Phone: q31-45-5767503, Fax: q31-45-5766255, E-mail: m.leers@atriummc.nl Keywords: cholesterol; exudate; lactate dehydro- genase (LDH) activity; pleural fluid; total protein; transudate. Introduction Pleural effusion is a common clinical entity which develops in thoracic or systemic diseases. Differen- tiating a pleural effusion as being either a transudate or an exudate is the first step in establishing the cause of a pleural effusion. Defining an effusion as a transu- date limits the differential diagnosis and the need for further diagnostic procedures. A transudate is due to systemic factors that influence the formation and absorption of pleural fluid. Thus, neither bacteriologic or cytologic studies of the pleural fluid nor pleural biopsy are initially indicated (1). In contrast, exudates more closely resemble plasma, as an exudate is the result of increased permeability of lung capillaries to protein, due to pleural inflammation or lymphatic obstruction. For this reason, an exudative pleural effu- sion often leads to more extensive and invasive diag- nostic procedures (2–6). Widely used criteria to discriminate exudative from transudative pleural effusions were proposed by Light and his co-workers more than 30 years ago (7): a pleu- ral fluid to serum total protein ratio )0.5, a fluid lac- tate dehydrogenase (LDH) activity )200 U/L, or a fluid to serum LDH ratio )0.6 was sufficient to classify an effusion as exudative, with the remaining fluids being transudates. Since then many reports have described modifications of the cutoff points used by Light and co-workers to improve specificity, because the origi- nal Light criteria misclassified an important number of pleural transudates as exudates (1, 8–11). Misclassifying transudates as exudates may have serious adverse consequences, i.e., patients might undergo unnecessary invasive interventions such as thoracentesis, pleural biopsy, thoracoscopy or thora- cotomy. These interventions are not free of morbidity if performed in patients with a systemic disorder such as heart, renal or hepatic failure. For that reason, sev- eral other parameters have been tested to distinguish transudates from exudates, e.g., pleural fluid to serum bilirubin ratio (12), pleural fluid cholinesterase (13), alkaline phosphatase (14), creatinine kinase, uric acid (15) and pleural fluid malondialdehyde (16). In 1987, Hamm and co-workers, assessed the diagnostic value of pleural cholesterol and found a significant lower concentration in patients with transudative than exudative pleural effusions (17). When using a cutoff level of 1.55 mmol/L, Guleria and co-workers reached a sensitivity of 88%, a specificity of 100% and an accur- acy of 92% for the identification of an exudative pleu- ral effusion (8). In contrast, Burgess et al. used the same criteria and cutoffs and reached a sensitivity of Brought to you by | Karolinska Institute Authenticated Download Date | 5/23/15 12:56 PM